I am reading about platinum resistance in ovarian cancer. The papers state that increased Nucleotide excision repair may cause platinum resistance but I am not able to understand how. The platinum based chemotherapy works by the platinum binding to DNA, creating crosslinks which are recognised by DNA binding proteins which then recruits DNA repair pathway and clear any damage . The NER helps in doing this so how can increased NER lead to resistance to the platinum based drug???
Thanks beforehand :)
http://www.intechopen.com/books/ovarian-cancer-a-clinical-and-translational-update/molecular-mechanisms-of-platinum-resistance-in-ovarian-cancer#article-front
Vrushall
Platinum compounds are used to treat cancers of the ovaries (cisplatin or carboplatin) this has been a long standing treatment, however there are certain risk associated with the administration of such treatments. I have provide two evidence-based resources for you to increase your understanding of the administration of platinum based compounds.
http://www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/HealthProfessional/page6
Hi Vrushali,
To my understanding, NER will be activated after single-strand break of DNA induced by platinum in the setting of acquired resistance; if repair is unsuccessful, the cancer cells will enter apoptosis. Nevertheless, if the repair is successful, then the cancer cells survive. So when increased NER such as in the setting of ERCC1 hyper-expression or polymorphism state, more cancer cells will survive through an effective repair from the platinum adducts single strand break.
possibly due to activation or expression of DNA repair enzymes that repairs the damage in cancer cell and allow them to survive and proliferate.
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